Sampling of Glycan-Bound Conformers by the Anti-HIV Lectin Oscillatoria agardhii agglutinin in the Absence of Sugar

Lectins from different sources have been shown to interfere with HIV infection by binding to the sugars of viral‐envelope glycoproteins. Three‐dimensional atomic structures of a number of HIV‐inactivating lectins have been determined, both as free proteins and in glycan‐bound forms. However, details...

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Bibliographic Details
Published in:Angewandte Chemie 2015-05, Vol.127 (22), p.6562-6565
Main Authors: Carneiro, Marta G., Koharudin, Leonardus M. I., Ban, David, Sabo, T. Michael, Trigo-Mourino, Pablo, Mazur, Adam, Griesinger, Christian, Gronenborn, Angela M., Lee, Donghan
Format: Article
Language:eng ; ger
Subjects:
Anti-HIV-Lectine
Binding
Chemistry
Glycan
Grundzustand
HIV
Human immunodeficiency virus
Konformative Selektion
Lectins
NMR-Spektroskopie
Oscillatoria agardhii
Proteine
Proteins
Recognition
Sampling
Sugars
Three dimensional
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Summary:Lectins from different sources have been shown to interfere with HIV infection by binding to the sugars of viral‐envelope glycoproteins. Three‐dimensional atomic structures of a number of HIV‐inactivating lectins have been determined, both as free proteins and in glycan‐bound forms. However, details on the mechanism of recognition and binding to sugars are elusive. Herein we focus on the anti‐HIV lectin OAA from Oscillatoria agardhii: We show that in the absence of sugars in solution, both the sugar‐free and sugar‐bound protein conformations that were observed in the X‐ray crystal structures exist as conformational substates. Our results suggest that glycan recognition occurs by conformational selection within the ground state; this model differs from the popular “excited‐state” model. Our findings provide further insight into molecular recognition of the major receptor on the HIV virus by OAA. These details can potentially be used for the optimization and/or development of preventive anti‐HIV therapeutics. Virenerkennung: NMR‐spektroskopische Studien offenbaren, dass ein gegen HIV aktives Lectin Hochmannosezucker durch konformative Selektion im Grundzustand erkennt – entgegen dem verbreiteten Modell, das einen angeregten Zustand annimmt. In Abwesenheit von Zuckern existieren sowohl die durch Röntgenkristallographie beobachteten zuckerfreien als auch die zuckergebundenen Proteinkonformationen als konformative Subzustände in Lösung (siehe Bild).
ISSN:0044-8249
1521-3757
DOI:10.1002/ange.201500213